Interleukin-1 Pathways in Cancer and Inflammation

Interleukin-1 (IL-1) represents a pivotal cytokine family at the crossroads of innate immunity, inflammation and tumour biology. The two principal agonists, IL-1α and IL-1β, are produced by myeloid and stromal cells and signal through a shared receptor (IL-1R1), triggering intracellular cascades such as NF-κB and MAPK. IL-1β maturation requires inflammasome assembly and caspase-1 activity, whereas IL-1α can exert effects in its precursor form. Under acute conditions, IL-1 drives host defence and tissue repair; chronic or dysregulated IL-1 signalling fosters a microenvironment conducive to angiogenesis, extracellular matrix remodelling, tumour cell proliferation, invasion and immunosuppression. Within the tumour microenvironment, IL-1 promotes recruitment of myeloid-derived suppressor cells and tumour-associated macrophages, enhances vascular permeability and stimulates pro-metastatic gene expression. The natural IL-1 receptor antagonist (IL-1Ra) and engineered inhibitors of IL-1β or inflammasome components have shown therapeutic promise in dampening pathological inflammation and tumour progression. Together, these findings underscore the dualistic nature of IL-1 in health and disease and highlight its status as a global target for interventions in cancer and inflammatory disorders.

Research from Nature Portfolio

Recent studies have elucidated the spatial and functional importance of caspase-1–mediated IL-1β processing in the triple-negative breast cancer setting. In these models, tumour-intrinsic expression of caspase-1, driven by ETS1 and counter-regulated by oestrogen receptor α, governs the recruitment of pro-tumoral macrophages and exclusion of cytotoxic T cells from tumour nests. Genetic and pharmacological inhibition of caspase-1 reconfigures the tumour immune landscape, converting an immunosuppressive microenvironment into one permissive for checkpoint-blockade efficacy. These findings reveal a mechanistic link between inflammasome activation and spatial immune architecture, offering a novel axis for therapeutic targeting in refractory solid tumours.

Interleukin-1 Pathways in Cancer and Inflammation publication trend

The graph below shows the total number of articles in interleukin-1 pathways in cancer and inflammation across all publications each year (not limited to Nature Index journals).

Technical terms

Inflammasome: A multi-protein intracellular complex that activates caspase-1 to process pro-IL-1β into its mature, secreted form.

Caspase-1: An enzyme that cleaves pro-IL-1β and pro-IL-18, triggering their release and initiating inflammatory signalling.

Tumour microenvironment: The cellular and molecular milieu surrounding tumour cells, including immune, stromal and vascular components.

IL-1 receptor antagonist (IL-1Ra): A naturally occurring inhibitor that binds IL-1 receptors without activating downstream signalling, tempering IL-1 responses.

Myeloid-derived suppressor cells (MDSCs): A heterogeneous population of immature myeloid cells that inhibit anti-tumour immunity and promote tumour progression.

References

1. Caspase-1-dependent spatiality in triple-negative breast cancer and response to immunotherapy. Nature Communications (2024).
2. The role of interleukin-1 in general pathology. Inflammation and Regeneration (2019).
3. Interleukin-1 Beta—A Friend or Foe in Malignancies?. International Journal of Molecular Sciences (2018).
4. Roles of IL-1 in Cancer: From Tumor Progression to Resistance to Targeted Therapies. International Journal of Molecular Sciences (2020).
5. Interleukin-1 and cancer progression: the emerging role of interleukin-1 receptor antagonist as a novel therapeutic agent in cancer treatment. Journal of Translational Medicine (2006).